Publications by authors named "Xu W"

19,056 Publications

S-ketamine alleviates carbon tetrachloride-induced hepatic injury and oxidative stress by targeting the Nrf2/HO-1 signaling pathway.

Can J Physiol Pharmacol 2021 Jul 26. Epub 2021 Jul 26.

Shengli Oilfield Central Hospital, 499782, Dongying, China, 257034;

The aim of the present study was to investigate the protective effect of S-ketamine (S-KET) against carbon tetrachloride (CCl4)-induced liver damage and oxidative stress, as well as to elucidate the related underlying mechanisms. Blood was collected to measure biochemical parameters (ALT, AST, ALP, TB and γ-GT) and the liver was harvested for histopathological analysis of enzymes related to the antioxidant response (MDA, SOD, GSH, and GSH-PX). Liver cell apoptosis was evaluated using the TUNEL assay. In addition, the expression levels of apoptosis-related proteins and the Nrf2/HO-1 signaling pathway were detected by western blot analysis to explore potential mechanisms. S-KET protected the liver from CCl4-induced damage. The changes to the liver biochemical parameters (increased ALT, AST, ALP, TB, and γ-GT) and oxidative stress-related indicators (increased MDA; depleted SOD, GSH, and GSH-PX) induced by CCl4 were inhibited by S-KET. S-KET also inhibited CCl4-induced cell apoptosis, the changes in expression of related proteins, and blocked CCl4-induced liver injury and oxidative stress via activation of the Nrf2/HO-1 signaling pathway. S-KET effectively protected the liver by inhibition of CCl4-induced damage via up-regulation the Nrf2/HO-1 signaling pathway.
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http://dx.doi.org/10.1139/cjpp-2020-0763DOI Listing
July 2021

An integrated safety analysis of treatment-emergent fungal infections in patients with psoriasis treated with ixekizumab from 16 clinical studies.

J Eur Acad Dermatol Venereol 2021 Jul 26. Epub 2021 Jul 26.

Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Interleukin (IL)-17 plays a role in host defense against common extracellular pathogens, including fungi. Biologics that selectively target IL-17 have shown efficacy in the treatment of psoriasis..
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http://dx.doi.org/10.1111/jdv.17554DOI Listing
July 2021

Direction Matters: On Influence-Preserving Graph Summarization and Max-Cut Principle for Directed Graphs.

Neural Comput 2021 Jul;33(8):2128-2162

RIKEN, Center for Advanced Intelligence Report, Tokyo 103-0027, Japan, and University of Tokyo, Tokyo 113-0033, Japan

Summarizing large-scale directed graphs into small-scale representations is a useful but less-studied problem setting. Conventional clustering approaches, based on Min-Cut-style criteria, compress both the vertices and edges of the graph into the communities, which lead to a loss of directed edge information. On the other hand, compressing the vertices while preserving the directed-edge information provides a way to learn the small-scale representation of a directed graph. The reconstruction error, which measures the edge information preserved by the summarized graph, can be used to learn such representation. Compared to the original graphs, the summarized graphs are easier to analyze and are capable of extracting group-level features, useful for efficient interventions of population behavior. In this letter, we present a model, based on minimizing reconstruction error with nonnegative constraints, which relates to a Max-Cut criterion that simultaneously identifies the compressed nodes and the directed compressed relations between these nodes. A multiplicative update algorithm with column-wise normalization is proposed. We further provide theoretical results on the identifiability of the model and the convergence of the proposed algorithms. Experiments are conducted to demonstrate the accuracy and robustness of the proposed method.
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http://dx.doi.org/10.1162/neco_a_01402DOI Listing
July 2021

High-Pressure Structural Evolution of Disordered Polymeric CS.

J Phys Chem Lett 2021 Jul 26:7229-7235. Epub 2021 Jul 26.

Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei, 230031, China.

Carbon disulfide is an archetypal double-bonded molecule belonging to the class of group IV-group VI, AB compounds. It is widely believed that, upon compression to several GPa at room temperature and above, a polymeric chain of type (-(C═S)-S-), named Bridgman's black polymer, will form. By combining optical spectroscopy and synchrotron X-ray diffraction data with ab initio simulations, we demonstrate that the structure of this polymer is different. Solid molecular CS polymerizes at ∼10-11 GPa. The polymer is disordered and consists of a mixture of 3-fold (C3) and 4-fold (C4) coordinated carbon atoms with some C═C double bonds. The C4/C3 ratio continuously increases upon further compression to 40 GPa. Upon decompression, structural changes are partially reverted, while the sample also undergoes partial disproportionation. Our work uncovers the nontrivial high-pressure structural evolution in one of the simplest molecular systems exhibiting molecular as well as polymeric phases.
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http://dx.doi.org/10.1021/acs.jpclett.1c01762DOI Listing
July 2021

Association of cardiovascular risk burden with risk of dementia and brain pathologies: A population-based cohort study.

Alzheimers Dement 2021 Jul 26. Epub 2021 Jul 26.

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

Introduction: The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies.

Methods: Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies.

Results: The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12).

Conclusions: A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.
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http://dx.doi.org/10.1002/alz.12343DOI Listing
July 2021

[Promotion and Mechanisms of DOM on Copper Adsorption by Suspended Sediment Particles].

Huan Jing Ke Xue 2021 Aug;42(8):3837-3846

College of Environmental Science and Engineering, Hunan University, Changsha 410082, China.

The adsorption of heavy metals by suspended sediment particles is a key process in the migration of heavy metals in lakes and is affected by various environmental conditions. To reveal the effects and mechanisms of dissolved organic matter (DOM) on the adsorption of copper ions by suspended sediment particles, a Cu(Ⅱ) adsorption test was conducted through a laboratory simulation test. The results showed that DOM promoted the adsorption of Cu(Ⅱ) onto the suspended particles. Under the respective influences of fulvic acid and DOM extracted from the sediment of the Xiangjiang River, the adsorption percentage of Cu(Ⅱ) increased from 71.51% to 75.31% and 85.69%. Scanning electron microscope-energy spectroscopy results showed that under the influence of DOM, Cu(Ⅱ) existed inside the sediment particles after being adsorbed. The results of UV-visible (UV-Vis) spectroscopy showed that Cu(Ⅱ) and DOM were first complexed and then dissociated during the adsorption reaction. The results of fluorescent excitation-emission matrix spectroscopy combined with parallel factor analysis and synchronous fluorescence spectroscopy combined with two-dimensional correlation analysis indicate that protein-like components promoted the adsorption of Cu(Ⅱ) onto the sediment suspended particles. In particular, tyrosine-like components played a critical role in promoting adsorption. However, humic-like components hardly promote this adsorption. This study has improved the theory of heavy metal migration in lakes and can be used as a basis for the prevention and control of heavy metal pollution in sediments.
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http://dx.doi.org/10.13227/j.hjkx.202012017DOI Listing
August 2021

[Comparison of early effectiveness of arthroscopic suture bridge technique and conventional double tunnel suture technique in treatment of avulsion fracture of posterior cruciate ligament insertion].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jul;35(7):829-835

Department of Orthopedics, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou Fujian, 363000, P.R.China.

Objective: To compare the early effectiveness of arthroscopic suture bridge technique and conventional double tunnel suture technique in the treatment of avulsion fracture of posterior cruciate ligament (PCL) insertion.

Methods: Between June 2013 and December 2018, 62 patients with tibial avulsion fracture of PCL insertion that met the criteria were selected and randomly divided into trial group (using arthroscopic suture bridge technique) and control group (using conventional double tunnel suture technique), 31 cases in each group. There was no significant difference in gender, age, injured side, cause of injury, time from injury to operation, Meyers & McKeever classification, Kellgren-Lawrence classification, and preoperative knee range of motion, difference of posterior relaxation of bilateral knee joints, International Knee Documentation Committee (IKDC) score, and Lysholm score between the two groups ( >0.05). The operation time and IKDC score, Lysholm score, knee range of motion, the difference of posterior relaxation of bilateral knee joints (measured by KT-2000 under knee flexion of 90° and 30 lbs) were recorded and compared between the two groups before operation and at 3 and 12 months after operation.

Results: Both groups successfully completed the operation, and the operation time of the trial group and the control group were (61.81±6.83) minutes and (80.42±4.22) minutes respectively, showing significant difference between the two groups ( =12.911, =0.000). All the incisions healed by first intention, and there was no wound infection and other early postoperative related complications. All patients were followed up 13-18 months (mean, 14.6 months). The fractures in both groups healed at 3 months after operation. No knee pain, limited movement, or other complications occurred. At 3 and 12 months after operation, the IKDC score, Lysholm score, knee range of motion, and the difference of posterior relaxation of bilateral knee joints in both groups were significantly improved when compared with preoperative ones, and further improved at 12 months after operation when compared with at 3 months after operation ( <0.05). At each time point after operation, the above indexes and the grade of the difference of posterior relaxation of bilateral knee joints in the trial group were significantly better than those in the control group ( <0.05).

Conclusion: Arthroscopic suture bridge technique in the treatment avulsion fracture of PCL insertion is simple and reliable, which can significantly improve the function and stability of the knee joint and obtain satisfactory early effectiveness.
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http://dx.doi.org/10.7507/1002-1892.202102080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311220PMC
July 2021

Ferrous ions doped layered double hydroxide: smart 2D nanotheranostic platform with imaging-guided synergistic chemo/photothermal therapy for breast cancer.

Biomater Sci 2021 Jul 26. Epub 2021 Jul 26.

Key Laboratory of Advanced Materials, Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China and State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

Developing simple and efficient nanotheranostic platforms with behavior responsive to the acid microenvironment of a tumor is of great significance for accurate tumor diagnosis and therapy. In this study, a smart 2D nanotheranostic platform has been successfully fabricated by doping functional ferrous ions into as-synthesized MgAl-layered double hydroxide (LDH) with doxurubicin (DOX) loading to form Fe-LDH/DOX NPs, which achieved magnetic resonance imaging (MRI)-guided synergistic chemo/photothermal therapy for breast cancer. The doping of ferrous ions into Fe-LDH/DOX enabled a strong photo-induced heating ability with a high photothermal conversion efficiency of 45.67%, which could be combined with the antitumor drug DOX to achieve the synergistic effect of photothermal therapy (PTT) and chemotherapy for killing tumor cells. Additionally, its in vitro pH-dependent degradation behavior and T2-weighted MRI effect revealed that the as-prepared Fe-LDH/DOX is sensitive to the tumor acid microenvironment. Most importantly, the growth rate of tumors in 4T1 bearing mice could be effectively inhibited after the synergistic treatment of PTT and chemotherapy by Fe-LDH/DOX. These results show that doping functional metal ions into LDH NPs may open a novel approach to fabricating an LDH NP-based nanotheranostics platform with advanced diagnostic and therapeutic performances.
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http://dx.doi.org/10.1039/d1bm00765cDOI Listing
July 2021

Multidisciplinary team therapy for left giant adrenocortical carcinoma: A case report.

World J Clin Cases 2021 Jul;9(20):5737-5743

Department of Urology, The Second Affiliated Hospital, University of South China, Hengyang 421001, Hunan Province, China.

Background: Adrenocortical carcinoma (ACC) is a rare malignant epithelial tumor originating from adrenocortical cells that carries a very poor prognosis. Metastatic or inoperable diseases are often considered incurable, and treatment remains a challenge. Especially for advanced cases such as ACC complicated with renal venous cancer thrombus, there are few cumulative cases in the literature.

Case Summary: The patient in this case was a 39-year-old middle-aged male who was admitted to the hospital for more than half a month due to dizziness and chest tightness. Computed tomography (CT) findings after admission revealed a left retroperitoneal malignant space-occupying lesion, but the origin of the formation of the left renal vein cancer thrombus remained to be determined. It was speculated that it originated from the left adrenal gland, perhaps a retroperitoneal source, and left adrenal mass + left nephrectomy + left renal vein tumor thrombus removal + angioplasty were performed under general anesthesia. Postoperative pathology results indicated a diagnosis of ACC. Postoperative steroid therapy was administered. At 3 mo after surgery, abdominal CT reexamination revealed multiple enlarged retroperitoneal lymph nodes and multiple low-density shadows in the liver, and palliative radiotherapy and mitotane were administered, considering the possibility of metastasis. The patient is currently being followed up.

Conclusion: ACC is a highly malignant tumor. Even if the tumor is removed surgically, there is still the possibility of recurrence. Postoperative mitotane and adjuvant chemoradiotherapy have certain benefits for patients, but they cannot fully offset the poor prognosis of this disease.
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http://dx.doi.org/10.12998/wjcc.v9.i20.5737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281393PMC
July 2021

Smart and Functionalized Development of Nucleic Acid-Based Hydrogels: Assembly Strategies, Recent Advances, and Challenges.

Adv Sci (Weinh) 2021 07 7;8(14):2100216. Epub 2021 May 7.

Key Laboratory of Precision Nutrition and Food Quality Department of Nutrition and Health China Agricultural University No. 17, Qinghua East Road Beijing 100083 China.

Nucleic acid-based hydrogels that integrate intrinsic biological properties of nucleic acids and mechanical behavior of their advanced assemblies are appealing bioanalysis and biomedical studies for the development of new-generation smart biomaterials. It is inseparable from development and incorporation of novel structural and functional units. This review highlights different functional units of nucleic acids, polymers, and novel nanomaterials in the order of structures, properties, and functions, and their assembly strategies for the fabrication of nucleic acid-based hydrogels. Also, recent advances in the design of multifunctional and stimuli-responsive nucleic acid-based hydrogels in bioanalysis and biomedical science are discussed, focusing on the applications of customized hydrogels for emerging directions, including 3D cell cultivation and 3D bioprinting. Finally, the key challenge and future perspectives are outlined.
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http://dx.doi.org/10.1002/advs.202100216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292884PMC
July 2021

The CT morphological characteristics and the clinical management strategy of posterior malleolar fractures with talar subluxation.

Am J Transl Res 2021 15;13(6):6478-6487. Epub 2021 Jun 15.

Department of Orthopaedics, The Second Affiliated Hospital of Soochow University Suzhou 215004, Jiangsu Province, China.

Background: The optimal clinical treatment and the computed tomography (CT) morphological characteristics of posterior malleolar fractures (PMF) with talar subluxation remain inconclusive. Clinically, both plate screws and lag screws are widely used to fix posterior malleolar fragments using a direct or indirect approach. We sought to summarize the morphological characteristics and modified classification on the basis of CT and the intraoperative strategy for posterior talar subluxation in PMF.

Methods: Retrospectively, 46 adult PMF patients with subluxations of the talus were recruited as the study cohort. According to its morphological features, PMF with subluxation of the talus can be divided mainly into two types using this modified classification: a complete fracture (the single-fragment type) and PMF with two-angled fracture fragments (the double-fragment type). The cohort's demographic information, classifications, fracture morphology, fixation methods, pain levels, and functional scores were recorded for both fracture types.

Results: The average values of the depths and heights of the posterior malleolar fragments were (29.1±7.3) mm for the single-fragment type and (17.9±4.2) mm for the double-fragment type. There was a significant difference in the mean values between the two types ( < 0.05). Posterior plate fixation was suitable for the single-fragment type, while antero-posterior and postero-anterior (AP-PA) lag screws fixations were made available for the double-fragment type. Both methods achieved good results. No significant differences were found in terms of sex, age, body mass index (BMI), side, Haraguchi classification, Bartoníček and Rammelt classification, Visual Analog Scale (VAS) scores, or American Orthopedic Foot & Ankle Society scores (AOFAS) when comparing the single-/double-fragment type groups after the mid-term follow-up ( > 0.05).

Conclusion: According to the injury mechanism and the morphological characteristics of the fractures, the proposed improved classification system for PMF with subluxation of the talus based on the injury mechanism and the fracture morphology can provide guidance for surgical management strategies and achieve optimal outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290741PMC
June 2021

The serum CK17 and CK19 expressions in cervical cancer patients and their prognostic value.

Am J Transl Res 2021 15;13(6):6439-6445. Epub 2021 Jun 15.

Department of Pathology, Zhejiang North Medical Center (Huzhou Central Hospital) Huzhou 313003, Zhejiang Province, China.

Objective: This study was designed to quantify the serum CK17 and CK19 expressions in cervical cancer (CC) patients and determine their predictive value.

Methods: A total of 124 CC patients admitted to Zhejiang North Medical Center (Huzhou Central Hospital) between November 2014 and November 2017 were recruited for the study and placed in a research group (the Res group), and 99 healthy individuals during the same period were also recruited for the study and placed in a control group (the Con group). Their serum CK17 and CK19 expressions were quantified, and the diagnostic significance of the two for CC was analyzed. Additionally, the patients were followed up for three years. The patients were then assigned to favorable and unfavorable prognosis groups, and then the predictive significance of CK17 and CK19 for such patients was evaluated.

Results: The Res group presented significantly higher serum CK17 and CK19 expression levels than the Con group, and the two factors were positively associated. Additionally, neither of the AUCs for serum CK17 and CK19 in identifying CC were less than 0.800, and the AUC of the combination of the two in identifying it was not smaller than 0.900. The AUC of the combination of serum CK17 and CK19 in identifying unfavorable CC prognoses was approximate 0.850, and high expression levels CK17 and CK19 were closely related with low three-year overall survival rates.

Conclusion: Serum CK17 combined with serum CK19 is of great diagnostic and predictive significance for CC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290704PMC
June 2021

Pink1/PARK2/mROS-Dependent Mitophagy Initiates the Sensitization of Cancer Cells to Radiation.

Oxid Med Cell Longev 2021 6;2021:5595652. Epub 2021 Jul 6.

NHC Key Laboratory of Radiobiology (Jilin University), School of Public Health, Jilin University, Changchun 130021, China.

Autophagy plays a double-edged sword for cancer; particularly, mitophagy plays important roles in the selective degradation of damaged mitochondria. However, whether mitophagy is involved in killing effects of tumor cells by ionizing radiation (IR) and its underlying mechanism remain elusive. The purpose is to evaluate the effects of mitochondrial ROS (mROS) on autophagy after IR; furthermore, we hypothesized that KillerRed (KR) targeting mitochondria could induce mROS generation, subsequent mitochondrial depolarization, accumulation of Pink1, and recruitment of PARK2 to promote the mitophagy. Thereby, we would achieve a new strategy to enhance mROS accumulation and clarify the roles and mechanisms of radiosensitization by KR and IR. Our data demonstrated that IR might cause autophagy of both MCF-7 and HeLa cells, which is related to mitochondria and mROS, and the ROS scavenger N-acetylcysteine (NAC) could reduce the effects. Based on the theory, mitochondrial targeting vector sterile - and HEAT/armadillo motif-containing protein 1- (Sarm1-) mtKR has been successfully constructed, and we found that ROS levels have significantly increased after light exposure. Furthermore, mitochondrial depolarization of HeLa cells was triggered, such as the decrease of NaK ATPase, CaMg ATPase, and mitochondrial respiratory complex I and III activities, and mitochondrial membrane potential (MMP) has significantly decreased, and voltage-dependent anion channel 1 (VDAC1) protein has significantly increased in the mitochondria. Additionally, HeLa cell proliferation was obviously inhibited, and the cell autophagic rates dramatically increased, which referred to the regulation of the Pink1/PARK2 pathway. These results indicated that mitophagy induced by mROS can initiate the sensitization of cancer cells to IR and might be regulated by the Pink1/PARK2 pathway.
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http://dx.doi.org/10.1155/2021/5595652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279859PMC
July 2021

Macrophages induce the expression of lncRNA ATB via the secretion of TGF-β to relieve ischemia-reperfusion injury in cardiomyocytes.

Exp Ther Med 2021 Sep 29;22(3):910. Epub 2021 Jun 29.

Department of Immunology, Basic and Forensic Medicine of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014040, P.R. China.

Cardiac ischemia-reperfusion can cause severe damage to cardiomyocytes. Previous studies have revealed that TGF-β can alleviate ischemia-reperfusion injury in cardiomyocytes by inducing the expression of long non-coding RNA (lncRNA) activated by TGF-β (ATB). However, M2 macrophages can secrete a large amount of TGF-β. However, whether M2 macrophages alleviate the ischemia-reperfusion-induced injury of cardiomyocytes by secreting TGF-β is unclear. In the present study, macrophages and cardiomyocytes were cultured under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to simulate ischemia-reperfusion injury. M2-type macrophage markers (IL-10, Arginase-1 and IL-13) were validated using reverse transcription-quantitative PCR and western blotting. Subsequently, the culture medium of M2-type macrophages was collected for the treatment of cardiomyocytes, which were cultured under OGD/R conditions. The levels of inflammatory factors and oxidase enzymes were detected with ELISA. The apoptotic rates of cardiomyocytes were detected by flow cytometry. The expression of cell apoptosis-related proteins and the phosphorylation levels of NF-κB were analyzed by western blotting. The expression levels of specific inflammatory cytokines and the levels of malondialdehyde and lactate dehydrogenase were suppressed in cardiomyocytes following treatment with culture medium derived from M2-type macrophages, which were cultured under OGD/R conditions. Furthermore, OGD/R-induced apoptosis of cardiomyocytes was also relieved following treatment of the cells with macrophage medium. It was found that M2-type macrophages could secrete TGF-β and that the culture medium of M2-type macrophages could activate the expression of lncRNA ATB in cardiomyocytes. TGF-β secreted by M2 macrophages relieved the inflammatory response, oxidative stress and apoptosis of cardiomyocytes by inducing the expression of lncRNA ATB.
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http://dx.doi.org/10.3892/etm.2021.10342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281357PMC
September 2021

Beta-2-Microglobulin is an Independent Risk Factor for Asymptomatic Carotid Atherosclerosis in Patients with Primary Aldosteronism.

J Atheroscler Thromb 2021 Jul 22. Epub 2021 Jul 22.

Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University.

Aim: To identify the association between serum beta-2-microglobulin (B2M) or cystatin C (CysC) and asymptomatic carotid atherosclerosis in patients with primary aldosteronism (PA).

Methods: In this cross-sectional study, 265 subjects were enrolled, including 83 patients with PA, 91 with essential hypertension (EH), and 91 normotensive (NT) controls. B2M, CysC, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured, and the aldosterone-to-renin ratio (ARR) was calculated. Carotid intima-media thickness (cIMT), increased cIMT, and presence of carotid plaque or carotid stenosis <50% in the carotid artery were measured via ultrasonography to evaluate the degree of asymptomatic carotid atherosclerosis.

Results: CIMT increased in the NT, EH, and PA groups (0.60 (0.50, 0.80) mm vs. 0.80 (0.60, 1.00) mm vs. 0.90 (0.70, 1.10) mm, P<0.01), so as the prevalence of increased cIMT and presence of carotid plaque (both P <0.05). The B2M and CysC levels exhibited the same trend (B2M: 1.60±0.34 mg/L, 1.80±0.41 mg/L, 1.98± 0.64 mg/L, P<0.05; CysC: 0.76±0.12 mg/L, 0.88±0.17 mg/L, 0.94±0.23 mg/L, P<0.05). B2M, CysC, PAC, and ARR were all positively associated with cIMT (all P<0.01) in the PA group. After adjusting for potential confounders, B2M, PAC, but not CysC or ARR were independently associated with increased cIMT and presence of carotid plaque and carotid stenosis <50%, respectively. The receiver operating characteristic (ROC) curve analysis revealed that B2M and PAC demonstrated significant predictive ability for increased cIMT and presence of carotid plaque and carotid stenosis <50%.

Conclusion: B2M is an independent risk factor for asymptomatic carotid atherosclerosis in patients with PA.
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http://dx.doi.org/10.5551/jat.62851DOI Listing
July 2021

Sustainable use of CRISPR/Cas in fish aquaculture: the biosafety perspective.

Transgenic Res 2021 Jul 25. Epub 2021 Jul 25.

Qingdao Vland Biotech Company Group, Qingdao, 266061, China.

Aquaculture is becoming the primary source of seafood for human diets, and farmed fish aquaculture is one of its fastest growing sectors. The industry currently faces several challenges including infectious and parasitic diseases, reduced viability, fertility reduction, slow growth, escapee fish and environmental pollution. The commercialization of the growth-enhanced AquAdvantage salmon and the CRISPR/Cas9-developed tilapia (Oreochromis niloticus) proffers genetic engineering and genome editing tools, e.g. CRISPR/Cas, as potential solutions to these challenges. Future traits being developed in different fish species include disease resistance, sterility, and enhanced growth. Despite these notable advances, off-target effect and non-clarification of trait-related genes among other technical challenges hinder full realization of CRISPR/Cas potentials in fish breeding. In addition, current regulatory and risk assessment frameworks are not fit-for purpose regarding the challenges of CRISPR/Cas notwithstanding that public and regulatory acceptance are key to commercialization of products of the new technology. In this study, we discuss how CRISPR/Cas can be used to overcome some of these limitations focusing on diseases and environmental release in farmed fish aquaculture. We further present technical limitations, regulatory and risk assessment challenges of the use of CRISPR/Cas, and proffer research strategies that will provide much-needed data for regulatory decisions, risk assessments, increased public awareness and sustainable applications of CRISPR/Cas in fish aquaculture with emphasis on Atlantic salmon (Salmo salar) breeding.
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http://dx.doi.org/10.1007/s11248-021-00274-7DOI Listing
July 2021

Comparative transcriptome analysis of Chinese grass shrimp (Palaemonetes sinensis) hepatopancreas under ectoparasitic isopod (Tachaea chinensis) infection.

Fish Shellfish Immunol 2021 Jul 22. Epub 2021 Jul 22.

Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 110866, Shenyang, China. Electronic address:

Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species. To better understand the interaction between shrimp immunity and isopod infection, we performed a transcriptome analysis of the hepatopancreas of Palaemonetes sinensis challenged with T. chinensis. After assembly and annotation, 75,980 high-quality unigenes were obtained using RNA-seq data. Differential gene expression analysis revealed 896 significantly differently expressed genes (DEGs) after infection, with 452 and 444 upregulated and downregulated genes, respectively. Specifically, expression levels of genes involved in detoxification, such as the interferon regulatory factor, venom carboxylesterase-6, serine proteinase inhibitor, and cytochrome P450, were upregulated. Furthermore, expression levels of genes corresponding to retinol dehydrogenase, triosephosphate isomerase, variant ionotropic glutamate receptor, and phosphoenolpyruvate carboxykinase were significantly upregulated after isopod parasitization, indicating that the shrimp's visual system was influenced by isopod parasitization. Moreover, quantitative real-time PCR of 10 DEGs helped validate the RNA-seq findings. These results provide a valuable basis for future studies on the elucidation of immune responses of P. sinensis to T. chinensis infection.
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http://dx.doi.org/10.1016/j.fsi.2021.07.018DOI Listing
July 2021

Powdered activated carbon-catalyzed chlorine oxidation of bisphenol-A and methylene blue: Identification of the free radical and effect of the carbon surface functional group.

Sci Total Environ 2021 Jul 17;797:149020. Epub 2021 Jul 17.

Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, No. 18 Shuangqing Road, Haidian District, Beijing 100085, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

The effect of powdered activated carbon (PAC) on chlorine oxidation is not well understood, therefore this study was designed to further investigate the chlorine oxidation mechanism with the presence of PAC. The oxidation processes of two model organic pollutants (bisphenol-A and methylene blue) with chlorine were compared in the absence and presence of PAC. The results showed a significant increase in reaction rates with the addition of PAC. Electron spin resonance indicated that the PAC catalyzed the oxidation of chlorine to generate more Cl and O. Additionally, the analysis of the surface characteristics of thermally modified PACs under N and their corresponding reaction rates revealed that there existed a significant correlation between the CO groups and the catalytic effect. PAC exhibited a much lower reaction rate under H modification, which indicated that the π electrons of the basal plane might be involved in the catalysis. Density functional theory calculations confirmed that the various oxygen groups on PAC reduced the activation barrier for HOCl dissociation, particularly the carboxyl group. This investigation provides a better understanding of the interactions between chlorine and activated carbon materials, which could be useful for selecting suitable water treatment agents.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149020DOI Listing
July 2021

Simultaneous determination of twenty-five compounds with anti-inflammatory activity in Spatholobi Caulis by using an optimized UFLC-MS/MS method: An application to pharmacokinetic study.

J Pharm Biomed Anal 2021 Jul 14;204:114267. Epub 2021 Jul 14.

Zhuzhou Qianjin Pharmaceutical Co., Ltd., Zhuzhou 412003, China.

As a kind of commonly used Traditional Chinese Medicine in clinical, Spatholobi Caulis (SPC) contains a wide variety of bioactive compounds, including protocatechuate (1), nicotinic acid (2), p-hydroxybenzoic acid (3), salicylic acid (4), 6,9-dihydroxy megastigma-4,7-dien-3-one (5), 8,9-dihydroxy megastigma-4,6-dien-3-one (6), daidzin (7), genistin (8), isolariciresinol (9), ononin (10), 4',8-dimethoxy-7-O-β-d-glucopyranosyl isoflavone (11), 3'-methoxydaidzein (12), odoratin (13), spasuberol A (14), (+)-pinoresinol (15), 4-hydroxy-3-methoxy cinnamic acid methyl ester (16), (+)-epipinoresinol (17), calycosin (18), 8-O-methylretusin (19), formononetin sodium (20), formononetin (21), biochanin A (22), butesuperin A (23), homovanillyl-4-oxo-nonanoate (24) and (6aR,11aR)-maackiain (25). The pharmacokinetic characteristics of these twenty-five compounds in rat plasma were quantitatively and simultaneously studied using a fast, sensitive and precise ultra fast liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method after oral administration of aqueous extract of SPC to rats. The mobile phase consists of acetonitrile and 0.5 mM ammonium acetate in water, and these compounds were well separated at a gradient elution program with flow rate of 0.35 mL/min. Carbamazepine was employed as the internal standard (IS) and all samples were precipitated with MeOH-ACN (2:1, v/v). The analytical method has been proved to be good linearity (R ≥ 0.9957), precise, accurate, stable, recovery and matrix effect, which applicated becomingly to study the pharmacokinetic processes of these compounds in rat plasma. In addition, these twenty-five compounds exhibited anti-inflammatory activity on the inflammatory model of NO over production in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Isoflavones, especially compounds 20-22 (The IC of which were 22.75 μM, 21.11 μM and 48.29 μM, respectively.) might be the important constituents for anti-inflammatory activity of SPC. This study provides reference values for the clinical application, in-depth study on new dosage forms and pharmacological activities of SPC.
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http://dx.doi.org/10.1016/j.jpba.2021.114267DOI Listing
July 2021

Genus Picrasma: A comprehensive review on its ethnopharmacology, phytochemistry and bioactivities.

J Ethnopharmacol 2021 Jul 22;280:114441. Epub 2021 Jul 22.

Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming, 650224, PR China. Electronic address:

Ethnopharmacological Relevance: The genus Picrasma belongs to the Simaroubaceae family and contains six species which are mainly distributed in tropical and subtropical regions of Asia and America. The barks, roots, stems, branches, or leaves of several Picrasma species have been applied as folk medicines to treat fever, sore throat, dysentery, eczema, nausea, loss of appetite, diabetes mellitus, cancer, and hypertension.

Aim Of The Study: A systematic summary on the botanic characterization, ethnopharmacological uses, phytochemistry, bioactivities and toxicity of species belonging to Picrasma was presented to facilitate the exploitation of the therapeutic potential of these plants.

Materials And Methods: The literatures about Picrasma were retrieved from a series of scientific search engines including Web of Science, SciFinder, PubMed, CNKI, Google Scholar, Elsevier, Wiley, ACS publications, and SpringerLink between 1970 and 2020. Plant names were validated by "The Plant List" (www.theplantlist.org).

Results: As ethnopharmacological uses, Picrasma species are valuable folk medicines to treat fever, inflammation, dysentery, eczema, cancer, diabetics, skin infection, and so on. Up to now, a total of 361 compounds including 126 alkaloids, 132 quassinoids, 67 triterpenoids, and 36 miscellaneous compounds were reported from Picrasma species. Quassinoids and alkaloids are the principal constituents in the genus. The extracts and phytochemical constituents of Picrasma species demonstrate a wide range of bioactivities including cytotoxic, anti-inflammatory, antimicrobial, and other activities.

Conclusions: Picrasma species are widely used as traditional medicines, have diverse chemical constituents with obvious biological activities. Nevertheless, further studies are required on the Picrasma species to assert the ethnopharmacological uses, clarify their bioactive constituents, determine pharmacological actions, and toxicity. Therefore, the present review may provide a critical clue for future studies and further exploitations on Picrasma species.
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http://dx.doi.org/10.1016/j.jep.2021.114441DOI Listing
July 2021

Novel mutation c.1210-3C > G in cis with a poly-T tract of 5T affects CFTR mRNA splicing in a Chinese patient with cystic fibrosis.

Front Med 2021 Jul 24. Epub 2021 Jul 24.

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
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http://dx.doi.org/10.1007/s11684-021-0846-5DOI Listing
July 2021

Can Watching Online Videos Be Addictive? A Qualitative Exploration of Online Video Watching among Chinese Young Adults.

Int J Environ Res Public Health 2021 Jul 6;18(14). Epub 2021 Jul 6.

Department of Psychology, School of Education, Soochow University, Suzhou 215123, China.

Watching online videos (including short-form videos) has become the most popular leisure activity in China. However, a few studies have reported the potential negative effects of online video watching behaviors (including the potential for 'addiction') among a minority of individuals. The present study investigated online video watching behaviors, motivational factors for watching online videos, and potentially addictive indicators of watching online videos. Semi-structured interviews were conducted among 20 young Chinese adults. Qualitative data were analyzed using thematic analysis. Eight themes were identified comprising: (i) content is key; (ii) types of online video watching; (iii) platform function hooks; (iv) personal interests; (v) watching becoming habitual; (vi) social interaction needs; (vii) reassurance needs; and (viii) addiction-like symptoms. Specific video content (e.g., mukbang, pornography), platform-driven continuous watching, and short-form videos were perceived by some participants as being potentially addictive. Specific features or content on Chinese online video platforms (e.g., 'Danmu' scrolling comments) need further investigation. Future studies should explore users' addictive-like behaviors in relation to specific types of online video content and their social interaction on these platforms.
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http://dx.doi.org/10.3390/ijerph18147247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306552PMC
July 2021

Integrative Transcriptomic and Proteomic Analysis Reveals an Alternative Molecular Network of Glutamine Synthetase 2 Corresponding to Nitrogen Deficiency in Rice ( L.).

Int J Mol Sci 2021 Jul 18;22(14). Epub 2021 Jul 18.

State Key Laboratory of Hybrid Rice, Wuhan University, Wuhan 430072, China.

Nitrogen (N) is an essential nutrient for plant growth and development. The root system architecture is a highly regulated morphological system, which is sensitive to the availability of nutrients, such as N. Phenotypic characterization of roots from LY9348 (a rice variety with high nitrogen use efficiency (NUE)) treated with 0.725 mM NHNO (1/4N) was remarkable, especially primary root (PR) elongation, which was the highest. A comprehensive analysis was performed for transcriptome and proteome profiling of LY9348 roots between 1/4N and 2.9 mM NHNO (1N) treatments. The results indicated 3908 differential expression genes (DEGs; 2569 upregulated and 1339 downregulated) and 411 differential abundance proteins (DAPs; 192 upregulated and 219 downregulated). Among all DAPs in the proteome, glutamine synthetase (GS2), a chloroplastic ammonium assimilation protein, was the most upregulated protein identified. The unexpected concentration of GS2 from the shoot to the root in the 1/4N treatment indicated that the presence of an alternative pathway of N assimilation regulated by GS2 in LY9348 corresponded to the low N signal, which was supported by GS enzyme activity and glutamine/glutamate (Gln/Glu) contents analysis. In addition, N transporters (, , , , , , , and putative ) and N assimilators (, , , , , and ) were significantly induced during the long-term N-deficiency response at the transcription level (14 days). Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that phenylpropanoid biosynthesis and glutathione metabolism were significantly modulated by N deficiency. Notably, many transcription factors and plant hormones were found to participate in root morphological adaptation. In conclusion, our study provides valuable information to further understand the response of rice roots to N-deficiency stress.
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http://dx.doi.org/10.3390/ijms22147674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304609PMC
July 2021

The Antiviral Molecule 5-Pyridoxolactone Identified Post BmNPV Infection of the Silkworm, .

Int J Mol Sci 2021 Jul 10;22(14). Epub 2021 Jul 10.

Biological Science Research Center, Southwest University, Chongqing 400715, China.

nucleopolyhedrovirus (BmNPV) is a pathogen that causes great economic losses in sericulture. Many genes play a role in viral infection of silkworms, but silkworm metabolism in response to BmNPV infection is unknown. We studied BmE cells infected with BmNPV. We performed liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based non-targeted metabolomics analysis of the cytosolic extract and identified 36, 76, 138, 101, 189, and 166 different molecules at 3, 6, 12, 24, 48, and 72 h post BmNPV infection (hpi) compared with 0 hpi. Compounds representing different areas of metabolism were increased in cells post BmNPV infection. These areas included purine metabolism, aminoacyl-tRNA biosynthesis, and ABC transporters. Glycerophosphocholine (GPC), 2-hydroxyadenine (2-OH-Ade), gamma-glutamylcysteine (γ-Glu-Cys), hydroxytolbutamide, and 5-pyridoxolactone glycerophosphocholine were continuously upregulated in BmE cells post BmNPV infection by heat map analysis. Only 5-pyridoxolactone was found to strongly inhibit the proliferation of BmNPV when it was used to treat BmE cells. Fewer infected cells were detected and the level of BmNPV DNA decreased with increasing 5-pyridoxolactone in a dose-dependent manner. The expression of BmNPV genes ie1, helicase, GP64, and VP39 in BmE cells treated with 5-pyridoxolactone were strongly inhibited in the BmNPV infection stage. This suggested that 5-pyridoxolactone may suppress the entry of BmNPV. The data in this study characterize the metabolism changes in BmNPV-infected cells. Further analysis of 5-pyridoxolactone, which is a robust antiviral molecule, may increase our understanding of antiviral immunity.
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http://dx.doi.org/10.3390/ijms22147423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307608PMC
July 2021

The differentiation of new human CD303 Plasmacytoid dendritic cell subpopulations expressing CD205 and/or CD103 regulated by Non-Small-Cell lung cancer cells.

Int Immunopharmacol 2021 Jul 20;99:107983. Epub 2021 Jul 20.

Department of Experimental and Clinical Immunology, CAS Lamvac Biotech Co., Ltd. Huangpu, Guangzhou, Guangdong, PR China. Electronic address:

CD303 plasmacytoid dendritic cells (pDCs) play an important role in the induction of immune tolerance and antitumor immunity. Here, we focused on the effect of NSCLC cells on the development of CD303 pDC subsets expressing CD205 and/or CD103. The NSCLC cell line H1299 and primary NSCLC cells were incubated with DCs. The protein expression of costimulatory molecules on CD303 pDCs, the production of pro-inflammatory and anti-inflammatory cytokines by CD303 pDCs and the development of CD303 pDC subsets were detected by using flow cytometry. Coculture with NSCLC cells modulates the protein expression of CD86 and HLA-DR on CD303 pDCs. Moreover, NSCLC cells suppressed the production of IL-12 and IL-23 but facilitated the secretion of IL-27 and TGF-β by CD303 pDCs. There were new CD303 pDC subsets expressing CD205 and/or CD103 in healthy donors and NSCLC patients: CD303CD205CD103, CD303CD205CD103, CD303CD205CD103 and CD303CD205CD103 pDCs. NSCLC cells modulated the differentiation of CD303 pDC subpopulations by regulating the protein expression of CD205 and/or CD103 on CD303 pDCs. NSCLC cells may regulate the immune functions of CD303 pDCs by modulating the expression of costimulatory molecules on DCs and the production of pro-inflammatory/anti-inflammatory cytokines by DCs. NSCLC cells also regulate the development of CD303 pDC subsets expressing CD205 and/or CD103. These outcomes may reveal a new cellular mechanism leading to the NSCLC-induced immune-suppressive microenvironment.
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http://dx.doi.org/10.1016/j.intimp.2021.107983DOI Listing
July 2021

Symptomatic spinal metastases from neuroendocrine neoplasms: surgical outcomes and prognostic analysis.

Clin Neurol Neurosurg 2021 May 27;207:106710. Epub 2021 May 27.

Department of Orthopedic Oncology, Changzheng Hospital, Shanghai, China. Electronic address:

Objectives: In this article, we investigated the efficiency of surgery in treating symptomatic spinal metastases from neuroendocrine neoplasms and performed univariate analysis for identification of possible prognostic factors.

Methods: A retrospective study was performed, enrolling a total of 19 patients who received surgeries in our center for symptomatic spinal metastases from neuroendocrine neoplasms (NEN). The Kaplan-Meier method was adopted to estimate overall survival (OS) and recurrence free survival (RFS). Univariate analysis was performed for identification of possible prognostic factors.

Results: All patients recruited displayed stable recovery after surgical intervention, with a median OS of 27.3 months (95% Confidence Interval: 16.4-38.1 months) and a median RFS of 23.0 months (95% Confidence Interval: 12.1-33.8 months). Postoperatively, 15 patients exhibited improved neurological function based on the Frankel classification, while 16 patients experienced significant pain relief, with mean visual analog scale (VAS) score decreasing from 7.47 ± 2.32-2.47 ± 1.25 (p < 0.05). Univariate analysis revealed that the presence of visceral metastases (p = 0.034) and extraspinal bone metastases (p = 0.016) are both related with poor prognosis. Additionally, well histologic differentiation (p = 0.010) and administration of postoperative octreotide (p = 0.041) or bisphosphonate (p = 0.023) are all indicators for better outcome.

Conclusions: Surgery is an efficient option for treating symptomatic spinal metastases from NEN due to its immediate and assured benefits in pain alleviation, restoration of function and stability reconstruction.
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http://dx.doi.org/10.1016/j.clineuro.2021.106710DOI Listing
May 2021

Leisure activity and cognitive function among Chinese old adults: The multiple mediation effect of anxiety and loneliness.

J Affect Disord 2021 Jul 17;294:137-142. Epub 2021 Jul 17.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun 130021, Jilin province, China. Electronic address:

Background: Most countries in the world, including China, are experiencing serious aging problems. The decline of cognitive function seriously affects the quality of life of the elderly in their later years and brings an inevitable heavy burden to the family and society. Therefore, in order to achieve successful aging, the purpose of this study is to test the serial multiple mediation effect of anxiety and loneliness between leisure activity and cognitive function in Chinese elderly population.

Methods: Using 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, we finally selected 6,525 Chinese elderly people over 65 years old after screening. Firstly, we described the basic social demographic information of the sample population. Secondly, Spearman correlation analysis was used to determine whether there is a correlation between leisure activity, anxiety, loneliness and cognitive function in Chinese elderly. Finally, the serial multiple mediation analysis was completed using the SPSS macro PROCESS program.

Results: Leisure activity, anxiety, loneliness and cognitive function were significantly correlated (p<0.01). Leisure activity can not only have a direct positive impact on the cognitive function of the elderly (effect=0.2231; SE=0.0122; 95%CI: LL=0.1992, UL=0.2470), but also have an indirect impact on the cognitive function through three paths: the independent mediating role of anxiety (effect=0.0028; SE=0.0015; 95%CI: LL=0.0001, UL=0.0059), the independent mediating role of loneliness (effect=0.0032; SE=0.0016; 95%CI: LL=0.0002, UL=0.0065), and the chain mediating role of anxiety and loneliness (effect=0.0008; SE=0.0004; 95%CI: LL=0.0001, UL=0.0017).

Limitations: All items were self-reported and some results may have biased. In the future, it may be more instructive to explore the impact of specific leisure activity on the cognitive function of the elderly.

Conclusions: The study suggests that leisure activity can improve cognitive function through decreasing anxiety and loneliness among the Chinese elderly. Diversified interventions aimed at increasing leisure activity participation in older adults would be beneficial for their mental health and cognitive function.
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http://dx.doi.org/10.1016/j.jad.2021.07.051DOI Listing
July 2021

Compartmentalization-aided interaction screening reveals extensive high-order complexes within the SARS-CoV-2 proteome.

Cell Rep 2021 Jul 17:109482. Epub 2021 Jul 17.

Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Beijing, China; Tsinghua-Peking Center for Life Sciences, Beijing, China; School of Life Sciences, Tsinghua University, Beijing, China. Electronic address:

Bearing a relatively large single-stranded RNA genome in nature, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes sophisticated replication/transcription complexes (RTCs), mainly composed of a network of nonstructural proteins and nucleocapsid protein, to establish efficient infection. In this study, we develop an innovative interaction screening strategy based on phase separation in cellulo, namely compartmentalization of protein-protein interactions in cells (CoPIC). Utilizing CoPIC screening, we map the interaction network among RTC-related viral proteins. We identify a total of 47 binary interactions among 14 proteins governing replication, discontinuous transcription, and translation of coronaviruses. Further exploration via CoPIC leads to the discovery of extensive ternary complexes composed of these components, which infer potential higher-order complexes. Taken together, our results present an efficient and robust interaction screening strategy, and they indicate the existence of a complex interaction network among RTC-related factors, thus opening up opportunities to understand SARS-CoV-2 biology and develop therapeutic interventions for COVID-19.
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http://dx.doi.org/10.1016/j.celrep.2021.109482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285250PMC
July 2021

Properties of a New Group of Cosmic Nuclei: Results from the Alpha Magnetic Spectrometer on Sodium, Aluminum, and Nitrogen.

Phys Rev Lett 2021 Jul;127(2):021101

Institute of Physics, Academia Sinica, Nankang, Taipei 11529, Taiwan.

We report the properties of sodium (Na) and aluminum (Al) cosmic rays in the rigidity range 2.15 GV to 3.0 TV based on 0.46 million sodium and 0.51 million aluminum nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. We found that Na and Al, together with nitrogen (N), belong to a distinct cosmic ray group. In this group, we observe that, similar to the N flux, both the Na flux and Al flux are well described by the sums of a primary cosmic ray component (proportional to the silicon flux) and a secondary cosmic ray component (proportional to the fluorine flux). The fraction of the primary component increases with rigidity for the N, Na, and Al fluxes and becomes dominant at the highest rigidities. The Na/Si and Al/Si abundance ratios at the source, 0.036±0.003 for Na/Si and 0.103±0.004 for Al/Si, are determined independent of cosmic ray propagation.
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http://dx.doi.org/10.1103/PhysRevLett.127.021101DOI Listing
July 2021

mA Regulator-Mediated Methylation Modification Model Predicts Prognosis, Tumor Microenvironment Characterizations and Response to Immunotherapies of Clear Cell Renal Cell Carcinoma.

Front Oncol 2021 6;11:709579. Epub 2021 Jul 6.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: This study aims to establish an N6-methyladenosine (mA) RNA methylation regulators-mediated methylation model and explore its role in predicting prognostic accuracy of immune contexture and characterizations of clear cell renal cell carcinoma (ccRCC).

Methods: The mA modification subclasses (mAMS) were identified by unsupervised cluster analysis and three clusters were determined by consensus clustering algorithm in a discovering cohort. Testing and real-world validation cohorts were used to identify predictive responses for immune checkpoint therapies (ICTs) of mAMS.

Results: Prognostic implications landscape of mA regulators in cancers and its differential expression levels in ccRCC patients were identified. Based on discovering cohort, ccRCC were automatically divided into three mAMS, and cluster 3 showed significant worse survival than cluster 1/2. Importantly, it was found that the immune checkpoint molecules expression was significantly elevated in cluster 3. Besides, mA score group (cluster 1&2) have significantly elevated TIDE score compared with mA score group (cluster 3). There was conspicuous tertiary lymphoid tissue, aggressive phenotype, elevated glycolysis, expression of PD-L1, abundance of CD8 T cells, CD4 FOXP3 Treg cells and TCRn immune cells infiltration in the high mA score group. Interestingly, there are significantly increased patients with clinical benefit in mA score group in 368 patients receiving ICTs from testing IMvigor210 (n = 292) and validation FUSCC (n = 55) cohorts.

Conclusion: Our discovery highlights the relationship between tumor epigenetic heterogeneity and immune contexture. Immune-rejection cluster 3 has pro-tumorigenic immune infiltration, and shows significant clinical benefits for ccRCC patients receiving ICTs, enabling patient selection for future clinical treatment.
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http://dx.doi.org/10.3389/fonc.2021.709579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290143PMC
July 2021
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